Liver Transplantation
Conditions
Keywords
tacrolimus, liver transplant, gene polymorphism, immunosuppressant
Brief summary
Genetic polymorphism and numerous clinical factors could influence tacrolimus pharmacokinetics, which led to large inter-and intra-individual variability.Since its narrow therapeutic range,predicting therapeutic outcome and individualized dosage remains to be a challenge. The study's objective is to identify the genetic and clinical factors that can influence clinical outcome in liver transplant.
Detailed description
A great number of studies had found significant correlation between tacrolimus pharmacokinetics and gene polymorphism. However, previous studies on the correlation between genetic factors and clinical outcome were controversial. Furthermore, most studies focused on single genetic polymorphism and clinical outcome, and very limited studies took multiple genetic factors and clinical factors into account. This is a retrospective study. Eligible patients were those who had signed informed consent for genetic study in previous research projects ( IRB approval number：201512005RINC and 201612023RIND ). The present study will collect laboratory data, concurrent medications, and therapeutic drug monitoring (TDM) data. Patient survival, graft survival, acute rejection and tacrolimus-associated adverse events will be assessed.
Interventions
None listed
Sponsors
National Taiwan University Hospital
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Eligible patients were those who had signed informed consent for genetic study in our previous research projects. Inclusion Criteria of the Previous Study: * patients who underwent living-donor liver transplantation during January 2008 to December 2017 * at the age of 20-65 * with tacrolimus-based immunosuppression after liver transplant for at least 6 months.
Exclusion criteria
of the Previous Study : * retransplantation * multi-organ transplantation * human immunodeficiency virus (HIV) positive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of patients with biopsy proven acute rejection (BPAR) | up to 12 months after liver transplantation | Incidence of BPAR will be estimated with Kaplan-Meier analysis |
| Graft survival | up to 9 years after liver transplantation | incidence of graft loss will be estimated Kaplan-Meier analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with tacrolimus-associated adverse events | up to 9 years after liver transplantation | Common adverse events of tacrolimus such as nephrotoxicity, post-transplant diabetes mellitus, hypertension, infection, hyperlipidemia and malignancy. * nephrotoxicity：decreased renal function estimated by glomerular filtration rate(GFR) using MDRD 4-Variable Equation * Post-transplant diabetes mellitus：defined by diagnosis and the use of antihyperglycemic agents, laboratory data including blood sugar(mg/dL) and hemoglobin A1c (percentage) * hypertension：defined by diagnosis and the use of antihypertensive agents, laboratory data including blood pressure(mmHg) * infection：defined by diagnosis of infection and the use of antiinfective agents * Hyperlipidemia：defined by diagnosis and the use of lipid-lowering agents, laboratory data including LDL (mg/dL), HDL (mg/dL) and total cholesterol (mg/dL) * malignancy：incidence of cancer |
| Patient survival | up to 9 years after liver transplantation | incidence of death |
Countries
Taiwan
Outcome results
None listed